MastocytosisPhase 2NCT00006413
Stem Cell Transplantation to Treat Systemic Mastocytosis
A Phase 2 study testing Stem cell transplantation in people with Mastocytosis, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial summary
This study will investigate the safety and effectiveness of an experimental stem cell transplant procedure for treating mastocytosis-a disease of abnormal mast cell growth. Patients often feel faint, have skin problems, joint and bone pain, low blood counts and enlarged liver, spleen or lymph nodes. Read more about this study
- Who is it for?
- Ages 2 to 80 years
- Conditions the study is for
- Mastocytosis
- What is being tested?
- Stem cell transplantation
- Type of treatment
- Surgery or procedure
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Oct 2000to 14 Dec 2006
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 80 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Ages greater than or equal to 2 to 80.
- Wt greater than 40 kg.
- Patients with systemic mastocytosis proven by a bone marrow biopsy and one of the following:
- Category I disease with poor prognosis secondary to extensive bone marrow involvement of mast cells (i.e. greater than 50 percent of the bone marrow cavity replaced by mast cells) and evidence of a bone marrow failure state defined as presence of one of the following for greater than or equal to 2 months:
- Neutrophil count less than 500/ mm3.
- Platelet count less than 20,000/mm3.
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- Dependency on transfusion of RBC or platelets.
- Category II disease with an associated hematologic disorder:
- Myelodysplastic syndromes.
- Myeloproliferative states except essential thrombocytosis or polycythemia vera.
- Increased blasts in peripheral blood or bone marrow greater than 10 percent.
- Bone marrow failure states as described above.
- Category III disease with enlarged peripheral lymph nodes with histopathological evidence of the replacement of the entire lymph node architecture with mast cells and/or accompanying peripheral eosinophilia. We also consider aggressive systemic mastocytosis with local tissue invasion as category III disease.
- Category IV disease with mast cell leukemia, characterized by the presence of malignant mast cells in the peripheral blood, which constitute greater than 10 percent of the nucleated cells.
- No major organ dysfunction precluding transplantation.
- DLCO greater than or equal to 65 percent predicted.
- Left ventricular ejection fraction of greater than or equal to 40%.
- ECOG performance status of 0 or 1.
- Life expectancy of more than 3 months.
- HLA-identical sibling available as donor.
- Patients or their parent(s)/responsible guardian(s) must be able to comprehend the investigational nature of the study and be willing to sign an informed consent.
- HLA identical family donor, (only HLA identical).
- Weight greater than or equal to 18 kg.
- Age less than or equal to 80 years old.
- Informed consent given.
Who cannot join
- Pregnant or lactating
- Age less than 2 or age greater than 80 years.
- Weight less than or equal to 40 kg.
- ECOG performance status of 2 or more.
- Psychiatric disorder or mental deficiency severe as to make compliance with the BMT treatment unlikely, and making informed consent impossible.
- Major anticipated illness or organ failure incompatible with survival from PBSC transplant.
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- DLCO less than 65 percent predicted.
- Left ventricular ejection fraction less than 40%.
- Baseline GFR less than 50ml/min: measured or calculated by the following formula: GFR = {(140-age) x body weight in kg}/72 x serum creatinine (for females, multiply by 0.85).
- Serum bilirubin greater than 4 mg/dl, transaminases greater than 5 times the upper limit of normal.
- Other malignant diseases liable to relapse or progress within 5 years.
- Life expectancy of less than 3 months.
- Pregnant or lactating.
- Donor unfit to receive G-CSF and undergo apheresis (Uncontrolled hypertension, history of congestive heart failure or unstable angina, thrombocytopenia).
- HIV positive. Donors who are positive for HBV, HCV or HTLV-1 may be used if the risk-benefit ratio is considered acceptable by the patient and investigator.
- Weight greater than 18 kg.
- Age greater than 2 or less than 80 years.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Low Intensity Preparative Regimen Followed by HLA-Matched, Mobilized Peripheral Blood Stem Cell Transplantation for Systemic Mastocytosis
This study will investigate the safety and effectiveness of an experimental stem cell transplant procedure for treating mastocytosis-a disease of abnormal mast cell growth. Patients often feel faint, have skin problems, joint and bone pain, low blood counts and enlarged liver, spleen or lymph nodes. As yet, there is no cure for mastocytosis, and treatment is aimed at controlling symptoms.
Stem cells are cells produced by the bone marrow that mature into the different blood components-white cells, red cells and platelets. Transplantation of allogeneic (donated) stem cells is a mainstay of therapy for some forms of leukemia. Patients first receive intensive chemotherapy and radiation to rid the body of cancer cells. This "conditioning" is followed by transplantation of donated stem cells to generate new, healthy bone marrow. In addition to producing the new bone marrow, the donated cells also fight any residual tumor cells that might have remained in the body. This is called a "graft-versus-tumor" effect. This study will examine whether a stem cell transplant from a healthy donor can similarly target and destroy mast cells in a "graft-versus-mast cell" effect. Also, to try to reduce the harmful side effects of chemotherapy and radiation, this study will use lower dose chemotherapy and no radiation.
Read more
Patients with advanced mastocytosis between 10 and 80 years old may be eligible for this study. They will be
tested for HLA type matching with a sibling and will undergo a medical history, physical examination and several tests to determine eligibility for the study.
Participants will undergo apheresis to collect lymphocytes (a type of white blood cell) for immune function tests. In this procedure, blood is drawn through a needle in the arm, similar to donating a unit of blood. The lymphocytes are then separated and collected by a cell separator machine, and the rest of the blood is returned through a needle in the other arm. Patients will also have a central venous line (flexible plastic tube) placed in their upper chest leading to a vein. This line will remain in place throughout the transplant and recovery period and will be used to transfuse blood components, administer medicines, infuse the donated stem cells, and draw blood for tests. Patients will begin conditioning with cyclophosphamide, starting 7 days before the transplant, and fludarabine, starting 5 days before the transplant, to prevent rejection of the donated cells. From 1 to 3 days after the chemotherapy is completed, the stem cells will be transfused through the central venous line. Also, from 4 days before the transplantation until about 3 months after the procedure, patients will receive cyclosporine and mycophenolate mofetil-drugs that help prevent both rejection of the donated cells and attack by the donor cells on the patient's cells (called graft-versus-host disease).
Patients will stay in the hospital about 20 to 30 days after the transplant. After discharge, they will continue to take antibiotics, cyclosporine and mycophenolate mofetil at home. If the mastocytosis progresses, cyclosporine and mycophenolate mofetil will be tapered over 4 weeks. If the mastocytosis persists, patients may receive additional transfusions of donor lymphocytes to help kill the mast cells.
Patients' progress will be followed weekly or twice weekly for 3 months, then at 6, 12, 18, 24, 30, 36, 48 and 60 months after transplant, and then twice a year for various tests, treatments and examinations.
Read the detailed description
Mastocytosis is a disease characterized by excessive numbers of mast cells in skin, bone marrow and internal organs such as liver, spleen and lymph nodes. Its genesis appears to be related to somatic mutations in c-kit, the receptor for mast cell growth factor. Although most patients present with the indolent form of the disease, approximately one-third of the patients have an associated hematologic disorder such as a myeloproliferative state or myelodysplastic syndrome. Patients with advanced forms of the disease, including those with an associated hematologic disorder have a poorer prognosis than those with indolent disease. There is no treatment known to cure or improve the natural course of mastocytosis. Since mast cells arise in the bone marrow from a CD34+ progenitor, bone marrow transplantation may offer the only hope for a cure.
In this protocol, we propose to treat patients with advanced forms of mastocytosis with an allogeneic stem cell transplant from an HLA-identical sibling, using a low intensity non-myeloablative regimen. This approach has the advantage of decreasing the transplant-related toxicity while allowing adequate immunosuppression to establish stem cell and lymphocyte engraftment. Donor derived CD4 and CD8 lymphocytes, which are important in killing of leukemic cells by mounting a "graft versus leukemia" effect, should be useful in the elimination of aberrant mast cells and their progenitors, that is "graft-versus-mast cell effect". This mechanism may be particularly relevant in mastocytosis as point mutations of c-kit may constitute an antigenically distinct T-cell target for recognition by the engrafted donor cells.
The primary end point of this study is regression of mastocytosis. The secondary end points are engraftment, hematologic response, degree of donor-host chimerism, incidence and severity of acute and chronic GVHD, transplant related morbidity and mortality, relapse, disease free survival, and overall survival.
- Conditions
- Mastocytosis
- Being tested
- Stem cell transplantation
- Keywords
- Peripheral Blood Stem Cells, Non-Myeloablative Bone Marrow Transplantation, Engraftment, Graft-versus-host Disease, Graft-Versus-Leukemia, Graft-Versus-Mast Cell, Cyclophosphamide, Fludarabine, Donor Apheresis, Mast Cells
- Medical subject headings
- Mastocytosis, Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stem cell transplantationProcedure or surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2000 (estimated)
- Study start13 Oct 2000
- Study completion14 Dec 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MastocytosisStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Enrolment
- 25 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00006413
- Sponsor's protocol ID
- 010010
- Other IDs
- 01-H-0010
- Status last verified
- 14 Dec 2006
- First submitted
- 17 Oct 2000
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Kirshenbaum AS, Goff JP, Semere T, Foster B, Scott LM, Metcalfe DD. Demonstration that human mast cells arise from a progenitor cell population that is CD34(+), c-kit(+), and expresses aminopeptidase N (CD13). Blood. 1999 Oct 1;94(7):2333-42.
PubMed 10498605
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Low Intensity Preparative Regimen Followed by HLA-Matched, Mobilized Peripheral Blood Stem Cell Transplantation for Systemic Mastocytosis
- ClinicalTrials.gov ID
- NCT00006413
- Acronym / sponsor ID
- 010010
- Conditions
- Mastocytosis
- Keywords
- Peripheral Blood Stem Cells, Non-Myeloablative Bone Marrow Transplantation, Engraftment, Graft-versus-host Disease, Graft-Versus-Leukemia, Graft-Versus-Mast Cell, Cyclophosphamide, Fludarabine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- 13 Oct 2000
- Study completion
- 14 Dec 2006
- First posted
- 18 Oct 2000 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will investigate the safety and effectiveness of an experimental stem cell transplant procedure for treating mastocytosis-a disease of abnormal mast cell growth. Patients often feel faint, have skin problems, joint and bone pain, low blood counts and enlarged liver, spleen or lymph nodes. As yet, there is no cure for mastocytosis, and treatment is aimed at controlling symptoms.
Stem cells are cells produced by the bone marrow that mature into the different blood components-white cells, red cells and platelets. Transplantation of allogeneic (donated) stem cells is a mainstay of therapy for some forms of leukemia. Patients first receive intensive chemotherapy and radiation to rid the body of cancer cells. This "conditioning" is followed by transplantation of donated stem cells to generate new, healthy bone marrow. In addition to producing the new bone marrow, the donated cells also fight any residual tumor cells that might have remained in the body. This is called a "graft-versus-tumor" effect. This study will examine whether a stem cell transplant from a healthy donor can similarly target and destroy mast cells in a "graft-versus-mast cell" effect. Also, to try to reduce the harmful side effects of chemotherapy and radiation, this study will use lower dose chemotherapy and no radiation.
Patients with advanced mastocytosis between 10 and 80 years old may be eligible for this study. They will be
tested for HLA type matching with a sibling and will undergo a medical history, physical examination and several tests to determine eligibility for the study.
Participants will undergo apheresis to collect lymphocytes (a type of white blood cell) for immune function tests. In this procedure, blood is drawn through a needle in the arm, similar to donating a unit of blood. The lymphocytes are then separated and collected by a cell separator machine, and the rest of the blood is returned through a needle in the other arm. Patients will also have a central venous line (flexible plastic tube) placed in their upper chest leading to a vein. This line will remain in place throughout the transplant and recovery period and will be used to transfuse blood components, administer medicines, infuse the donated stem cells, and draw blood for tests. Patients will begin conditioning with cyclophosphamide, starting 7 days before the transplant, and fludarabine, starting 5 days before the transplant, to prevent rejection of the donated cells. From 1 to 3 days after the chemotherapy is completed, the stem cells will be transfused through the central venous line. Also, from 4 days before the transplantation until about 3 months after the procedure, patients will receive cyclosporine and mycophenolate mofetil-drugs that help prevent both rejection of the donated cells and attack by the donor cells on the patient's cells (called graft-versus-host disease).
Patients will stay in the hospital about 20 to 30 days after the transplant. After discharge, they will continue to take antibiotics, cyclosporine and mycophenolate mofetil at home. If the mastocytosis progresses, cyclosporine and mycophenolate mofetil will be tapered over 4 weeks. If the mastocytosis persists, patients may receive additional transfusions of donor lymphocytes to help kill the mast cells.
Patients' progress will be followed weekly or twice weekly for 3 months, then at 6, 12, 18, 24, 30, 36, 48 and 60 months after transplant, and then twice a year for various tests, treatments and examinations.
Detailed description
Mastocytosis is a disease characterized by excessive numbers of mast cells in skin, bone marrow and internal organs such as liver, spleen and lymph nodes. Its genesis appears to be related to somatic mutations in c-kit, the receptor for mast cell growth factor. Although most patients present with the indolent form of the disease, approximately one-third of the patients have an associated hematologic disorder such as a myeloproliferative state or myelodysplastic syndrome. Patients with advanced forms of the disease, including those with an associated hematologic disorder have a poorer prognosis than those with indolent disease. There is no treatment known to cure or improve the natural course of mastocytosis. Since mast cells arise in the bone marrow from a CD34+ progenitor, bone marrow transplantation may offer the only hope for a cure.
In this protocol, we propose to treat patients with advanced forms of mastocytosis with an allogeneic stem cell transplant from an HLA-identical sibling, using a low intensity non-myeloablative regimen. This approach has the advantage of decreasing the transplant-related toxicity while allowing adequate immunosuppression to establish stem cell and lymphocyte engraftment. Donor derived CD4 and CD8 lymphocytes, which are important in killing of leukemic cells by mounting a "graft versus leukemia" effect, should be useful in the elimination of aberrant mast cells and their progenitors, that is "graft-versus-mast cell effect". This mechanism may be particularly relevant in mastocytosis as point mutations of c-kit may constitute an antigenically distinct T-cell target for recognition by the engrafted donor cells.
The primary end point of this study is regression of mastocytosis. The secondary end points are engraftment, hematologic response, degree of donor-host chimerism, incidence and severity of acute and chronic GVHD, transplant related morbidity and mortality, relapse, disease free survival, and overall survival.
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 2 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (25 listed)
- Ages greater than or equal to 2 to 80.
- Wt greater than 40 kg.
- Patients with systemic mastocytosis proven by a bone marrow biopsy and one of the following:
- Category I disease with poor prognosis secondary to extensive bone marrow involvement of mast cells (i.e. greater than 50 percent of the bone marrow cavity replaced by mast cells) and evidence of a bone marrow failure state defined as presence of one of the following for greater than or equal to 2 months:
- Neutrophil count less than 500/ mm3.
Key exclusion criteria (17 listed)
- Pregnant or lactating
- Age less than 2 or age greater than 80 years.
- Weight less than or equal to 40 kg.
- ECOG performance status of 2 or more.
- Psychiatric disorder or mental deficiency severe as to make compliance with the BMT treatment unlikely, and making informed consent impossible.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Stem cell transplantation | Procedure or surgery | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Background: PubMed 10498605Kirshenbaum AS, Goff JP, Semere T, Foster B, Scott LM, Metcalfe DD. Demonstration that human mast cells arise from a progenitor cell population that is CD34(+), c-kit(+), and expresses aminopeptidase N (CD13). Blood. 1999 Oct 1;94(7):2333-42.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Stem cell transplantation in people with Mastocytosis, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00006413, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2017.